1. Field of the Invention
The present invention relates to a treatment of a pancreatic disease with a 15-ketoprostaglandin compound.
Prostaglandins (hereinafter, prostaglandins are referred to as PGs) are members of a class of organic carboxylic acid that are contained in human and most other mammalian tissues or organs and that exhibit a wide range of physiological activities. Naturally occurring PGs possess as a common structural feature the prostanoic acid skeleton: ##STR1## Some synthetic analogues have somewhat modified skeletons. The primary PGs are classified based on the structural feature of the five-membered cycle moiety into PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGGs, PGHs, PGIs and PGJs, and also on the presence or absence of unsaturation and oxidation in the chain moiety as:
______________________________________ Subscript 1 13,14-unsaturated-15-OH Subscript 2 5,6- and 13,14-diunsaturated- 15-OH Subscript 3 5,6- 13,14- and 17,18- triunsaturated-15-OH ______________________________________
Further, PGFs are sub-classified according to the configuration of hydroxy group at 9 into .alpha.(hydroxy group being in the alpha configuration ) and .beta.(hydroxy group being in the beta configuration).
2. Background Information
PGE.sub.1, PGE.sub.2 and PGE.sub.3 are known to have vasodilating, hypotensive, gastro-juice reducing, intestinehyperkinetic, uterine contracting, diuretic, bronchodilating and anti-ulcer activities. Also, PGF.sub.1.alpha., PGF.sub.2.alpha. and PGF.sub.3.alpha. are known to have hypertensive, vasocontracting, intestine-hyperkinetic, uterine contracting, luteo-regressive and bronchocontracting activities.
U.S. Pat. No. 4,374,856 discloses the hepatocyte-protecting action of 15-methyl-PGE.sub.2 and 16,16-dimethyl-PGE.sub.2 . JP-A-164512/1983 discloses the activity of 15-(3-propylcyclo- pentyl)-16,17,18,19,20-pentanor-6-oxo-PGE.sub.1 methyl ester in the treatment of acute pancreatitis. JP-A-203911/1983 discloses the cell-protecting action of certain 6-oxo-PGE.sub.1 and PGI.sub.2 having methyl group(s) at one or two of positions 15, 16, 17 and 20 and specific 15-cyclopentyl-PGI.sub.1. All these compounds, however, do not belong to 15-keto-PGs or their derivatives.
European Patent Application No. 0,310,305 describes that 15-keto-PGs can be used as catharitics.
In addition, some 15-keto (i.e. having an oxo group at position 15 in place of the hydroxy group) prostaglandins and 13,14-dihydro-15-ketoprostaglandins are known as substances naturally produced by enzymatic actions during metabolism of primary PGs (Acta Physiologica Scandinavica, 66, 509, 1966). It has also been described that 15-ketoprostaglandin F2.alpha. has an antipregnant activity. However, it has not been reported that 15-ketoprostaglandin compounds are therapeutically effective in the treatment of a pancreatic disease.
The pancreatic disease includes acute pancreatitis, acute pancreatic necrosis, chronic pancreatitis, hereditary pancreatitis, and pancreatic cysts, some of which are not etiologically clarified. Effective medicament has not been found and there is a continuous need for developing agents for treatment of pancreatic disease.
As a result of extensive studies about the biological properties of 15-ketoprostaglandin compounds, the present inventors have discovered that these compounds have an activity of improving or recovering injured pancreatic function in the experimental acute pancreatitis model and therefore useful as an agent for treating pancreatic disease.